Assessing Nutrition-aligned Resmetirom Roll-out
试验速览
- 阶段
- 4 期
- 状态
- 尚未招募
- 入组人数
- 120
- 试验地点
- 1
- 主要终点
- MRI-PDFF change
研究概览
简要总结
This randomized control trial aims to evaluate the effectiveness of combining resmetirom therapy (first approved pharmacological therapy for treating metabolic dysfunction-associated steatohepatitis (MASH)) with a nutritional intervention compared to resmetirom therapy alone over one year in improving liver health among 120 patients living with non-cirrhotic MASH. We hypothesize that patients receiving resmetirom and nutritional intervention will experience more significant improvements in liver function than those receiving only resmetirom therapy.
详细描述
On March 14, 2024, resmetirom, a selective thyroid hormone receptor-β agonist, became the first pharmacological therapy approved by the US Food and Drug Administration (FDA) for treating metabolic dysfunction-associated steatohepatitis (MASH). Although, lifestyle modification remains first-line MASH treatment the provision of resmetirom is rarely accompanied by structured non-pharmacological interventions, and evidence guiding the integration of nutrition-based strategies with pharmacotherapy is limited. This study aims to evaluate the effectiveness of a nutrition-based intervention, including medically tailored meal (MTM) and nutrition education provision combined with resmetirom therapy, compared with resmetirom therapy combined with standard-of-care lifestyle recommendations, in improving liver function.
This multi-site, prospective, randomised controlled trial will enroll 120 adults (18-75 years) with non-cirrhotic MASH and fibrosis stages F2-F3. Recruited participants will undergo baseline assessments including evaluation of medical history and lifestyle behaviors, completion of a food frequency questionnaire, blood pressure measurement, blood sampling, anthropometric measurements (weight, height, and waist and hip circumference), and assessment of liver steatosis and fibrosis using imaging methods. Upon completion of baseline evaluations, participants will be randomised 1:1 to receive either: (1) resmetirom plus standard-of-care lifestyle education (control); or (2) resmetirom plus a structured nutritional intervention consisting of MTM delivery and lifestyle education (intervention).
The primary endpoints are changes in liver steatosis and fibrosis at 12 months, assessed by imaging methods. Secondary endpoints include changes in blood-circulating lipids, alanine aminotransferase levels, metabolic parameters, anthropometrics, dietary quality, and lifestyle behaviours. Analyses will follow an intention-to-treat approach using regression models adjusted for relevant covariates.
Adherence assessments will be conducted at 3, 6, and 9 months, with outcome evaluations at 6 months and at the end of the study (12 months).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Provide informed consent
- •Be 18-75 years old
- •Have non-cirrhotic MASH with fibrosis stage F2-F3 (VCTE 8-20 kPa and CAP =280 dB/m)
- •Be initiating resmetirom per standard of care
- •Be able to comply with study procedures, including fasting visits
- •Reside in one of the five New York City boroughs
排除标准
- •Have cirrhosis or decompensated liver disease
- •Have other chronic liver diseases
- •Are pregnant or breastfeeding
- •Consume alcohol above defined thresholds or have PEth =20 ng/mL
- •Have recent major surgery or hospitalization
- •Are on glucagon-like peptide-1 agonist therapy (e.g., exenatide, liraglutide, lixisenatide, albiglutide, dulaglutide, semaglutide and albiglutide), unless the dose is stable for 12 weeks prior to the baseline evaluation and they have not experienced a >5% weight loss in the 6 months preceding resmetirom initiation.
- •Are undergoing bariatric surgery
- •Are living with any other end-stage organ disease (e.g., heart, lung or kidney failure requiring dialysis) or have any active malignancy in the last 5 years.
- •Have conditions preventing consumption of provided meals
研究组 & 干预措施
Resmetirom plus medically tailored meals and lifestyle education
Participants receive resmetirom once daily by weight-based dosing (80 mg if <100 kg; 100 mg if ≥100 kg) plus 10 medically tailored meals per week based on Mediterranean-diet principles, along with online nutrition and physical activity education at baseline and follow-up.
干预措施: Resmetirom therapy (Drug)
Resmetirom plus standard-of-care lifestyle education
Participants receive the same resmetirom protocol once daily by weight-based dosing (80 mg if <100 kg; 100 mg if ≥100 kg), plus healthy diet and physical activity handouts and the option of a telehealth consultation with a dietitian.
干预措施: Resmetirom therapy (Drug)
Resmetirom plus medically tailored meals and lifestyle education
Participants receive resmetirom once daily by weight-based dosing (80 mg if <100 kg; 100 mg if ≥100 kg) plus 10 medically tailored meals per week based on Mediterranean-diet principles, along with online nutrition and physical activity education at baseline and follow-up.
干预措施: Comprehensive nutritional intervention (Behavioral)
Resmetirom plus standard-of-care lifestyle education
Participants receive the same resmetirom protocol once daily by weight-based dosing (80 mg if <100 kg; 100 mg if ≥100 kg), plus healthy diet and physical activity handouts and the option of a telehealth consultation with a dietitian.
干预措施: Standard dietary support (Behavioral)
结局指标
主要结局
MRI-PDFF change
时间窗: Baseline and 12 months
Magnetic resonance imaging derived proton-density-fat-fraction (MRI-PDFF) will be used to evaluate liver steatosis. Absolute change in MRI-PDFF (%) between the two groups at month 12, as an indicator for steatosis change
MRE change
时间窗: Baseline and 12 months
Magnetic resonance elastography (MRE) will be used to evaluate liver fibrosis. Absolute change in MRE (kPa) between the two groups at month 12
次要结局
- Controlled attenuation parameter (CAP) change(Baseline, 6 months and 12 months)
- Vibration-controlled transient elastography (VCTE) responder(Baseline, 6 months and 12 months)
- Plasma LDL-C responder(Baseline, 6 months and 12 months)
- Triglyceride responder(Baseline, 6 and 12 months)
- Apolipoprotein B change(Baseline, 6 and 12 months)
- Lp(α) change(Baseline, 6 and 12 months)
- ALT responder(Baseline, 6 and 12 months)
研究者
Jeffrey V. Lazarus
Professor of Global Health
City University of New York